Single molecule detection

Abstract

Disclosed herein is a method comprising patterning a second electrode of each of a plurality of electrode pairs onto a substrate; patterning a strip of a sacrificial layer directly across the second electrode; patterning a first electrode of each of the plurality of electrode pairs directly on the strip of the sacrificial layer; forming a nanogap channel by removing the strip of the sacrificial layer; wherein the strip of the sacrificial layer is sandwiched between and in direct contact with the first electrode and the second electrode before the strip is removed, and wherein at least a portion of the first electrode directly faces at least a portion of the second electrode. The method may involve planarization (e.g., CMP). The electrode pairs may be configured such that a redox active molecule can only diffuse back and forth therebetween while it is in the portion of the nanogap channel sandwiched therebetween.

What is claimed is: 
     
         1 . A method comprising:
 patterning a second electrode of each of a plurality of electrode pairs onto a substrate;   patterning a strip of a sacrificial layer directly across the second electrode;   patterning a first electrode of each of the plurality of electrode pairs directly on the strip of the sacrificial layer; and   forming a nanogap channel by removing the strip of the sacrificial layer;   wherein the strip of the sacrificial layer is sandwiched between and in direct contact with the first electrode and the second electrode before the strip is removed, and   wherein at least a portion of the first electrode directly faces at least a portion of the second electrode.   
     
     
         2 . The method of  claim 1 , wherein the first electrode and the second electrode are not electrically shorted. 
     
     
         3 . The method of  claim 1 , wherein the at least portion of first electrode and the at least portion of second electrode are exposed to an interior of the nanogap channel. 
     
     
         4 . The method of  claim 1 , wherein the nanogap channel has a height of 100 nm or less, 75 nm or less, 50 nm or less, 25 nm or less, 10 nm or less, 5 nm or less, or 1 nm or less. 
     
     
         5 . The method of  claim 1 , wherein the nanogap channel fluidically and sequentially extends across each of the plurality of electrode pairs. 
     
     
         6 . The method of  claim 1 , wherein the plurality of electrode pairs consist of two electrode pairs. 
     
     
         7 . The method of  claim 1 , wherein the plurality of electrode pairs consist of three electrode pairs. 
     
     
         8 . The method of  claim 1 , further comprising patterning a bioreactor. 
     
     
         9 . The method of  claim 8 , wherein the bioreactor is arranged such that all reaction products from the bioreactor flow into the nanogap channel and by the plurality of electrode pairs. 
     
     
         10 . The method of  claim 8 , wherein the bioreactor is inside the nanogap channel. 
     
     
         11 . The method of  claim 8 , wherein the bioreactor is an area with a functionalized surface. 
     
     
         12 . The method of  claim 8 , wherein a molecule is immobilized to the bioreactor, wherein the molecule is selected from a group consisting of a polymerase, a nuclease, a DNA or RNA strand, and a peptide. 
     
     
         13 . The method of  claim 1 , further comprising bonding a microfluidics chip comprising a bypass channel fluidically parallel with the nanogap channel. 
     
     
         14 . The method of  claim 1 , further comprising bonding an electric circuit to the plurality of electrode pairs through vias and microbumps. 
     
     
         15 . The method of  claim 1 , wherein a portion of the nanogap channel sandwiched between the at least portion of the first electrode and the at least portion of the second electrode has a length to width ratio of greater than 50:1, greater than 100:1, greater than 500:1, greater than 1000:1, or greater than 2000:1. 
     
     
         16 . A method comprising:
 forming a first electrode and a second electrode of each of a plurality of electrode pairs;   wherein the first electrode and the second electrode are separated by a nanogap channel;   wherein at least a portion of first electrode directly faces at least a portion of the second electrode; and   wherein the at least portion of first electrode and the at least portion of second electrode are exposed to an interior of the nanogap channel.   
     
     
         17 . The method of  claim 16 , wherein the at least portion of first electrode and the at least portion of second electrode are exposed to an interior of the nanogap channel. 
     
     
         18 . The method of  claim 16 , wherein the nanogap channel has a height of 100 nm or less, 75 nm or less, 50 nm or less, 25 nm or less, 10 nm or less, 5 nm or less, or 1 nm or less. 
     
     
         19 . The method of  claim 16 , wherein the nanogap channel fluidically and sequentially extends across each of the plurality of electrode pairs. 
     
     
         20 . The method of  claim 16 , wherein the plurality of electrode pairs consist of two electrode pairs. 
     
     
         21 . The method of  claim 16 , wherein the plurality of electrode pairs consist of three electrode pairs. 
     
     
         22 . The method of  claim 16 , further comprising bonding an electric circuit to the plurality of electrode pairs through vias and microbumps. 
     
     
         23 . A method comprising:
 forming a nanogap channel fluidically and sequentially extending across each of a plurality of electrode pairs;   wherein at least one electrode pair in the plurality of electrode pairs is configured to detect a redox cycling of a chemical species flowing in the nanogap channel.   
     
     
         24 . The method of  claim 23 , wherein the plurality of electrode pairs are configured to identify products of incorporation reactions of nucleotides into a complementary strand to a DNA molecule being sequenced. 
     
     
         25 . The method of  claim 23 , wherein the plurality of electrode pairs are configured to identify products of digestion of a DNA molecule being sequenced.